Biologically-enhanced sensor arrays for the analysis of proteins

蛋白质组学是对蛋白质的研究，包括对蛋白质结构和功能的研究。这包括研究哪些蛋白质被表达，何时何地表达，蛋白质的结构，蛋白质的作用以及蛋白质的相互作用。发现新的生物标志物和新药需要蛋白质组学仪器、试剂和测试。这类仪器的市场在2013年超过了50亿美元，预计到2019年将达到228亿美元。蛋白质的多重分析对于理解和诊断复杂疾病具有特别重要的意义，而传统的基因组分析有些不足。然而，传统技术涉及多个步骤，因此费时费力，不适合大规模血液筛查。因此，人们一直对开发绕过典型蛋白质微阵列限制的生物测定平台感兴趣。典型的生物测定系统将物理传感器与特定的识别探针（如酶、核酸、细胞、抗体或人工受体）耦合在一起。换能器由一个装置组成，该装置通过改变目标的一种物理特性来检测目标的存在。表面声波传感器在流体分析系统的部署中表现出几个优势。例如，重量生物分子检测为传统的朊病毒和蛋白质检测提供了强有力的替代方法。更具体地说，在剪切模式下工作的薄膜体声波谐振器（FBAR）传感器能够对流体中的分析物进行真实型检测，这是许多其他传感器平台所缺少的一个关键特性。为了使FBAR传感器能够用于分析液体中的蛋白质，必须解决几个挑战。首先，这种设备中使用的典型压电材料在接触液体时会降解。其次，刷新和重用传感器表面的能力将构成一项重要资产。最后，传感器的响应应针对病原体的检测做出特定的响应。该项目将通过以下目标来解决这些挑战：1)开发能够抵抗流体暴露的压电纳米材料和FBAR器件，2)开发可更新的表面部分，赋予蛋白质和朊病毒检测的特异性，以及3)将这些生物增强传感器与有源CMOS读出电路集成。该平台将为加拿大医疗保健和制药行业开辟新的机会。它将提高加拿大制药业开发和销售新药的能力，使人们能够更好地了解有关疾病，从而提高加拿大人的总体福祉。

Proteomics is the study of proteins, including the study of the structure and function of proteins. This includes the study of which proteins are expressed, when and where they are expressed, structure of proteins, roles of proteins, and interactions of proteins. Proteomic instruments, reagents and testing are needed to discover new biomarkers and new drugs. The market for such type of instrumentation topped $5 billion dollars in 2013 and is expected to reach $ 22.8 billion by 2019. The multiplexed assaying of proteins is of specific importance for the understanding and diagnosis of complex diseases where traditional genomic assays are somewhat inadequate. Traditional techniques however involves multiple steps and are thus labor consuming and inappropriate for large scale blood screening. There has therefore been sustained interest towards the development of bioassay platforms circumventing the limitations of typical proteins microarrays. A typical bioassay system couples a physical transducer with a specific recognition probe such as an enzyme, nucleic acid, cell, antibody or artificial receptor. The transducer consists of a device detecting the presence of the target through a change of one of its physical properties. Surface acoustic wave sensors exhibit several advantages for the deployment of analytical systems operating in fluids. For instance, gravimetric biomolecular detection offers potent alternatives to traditional assays for the detection of prions and proteins. More specifically, thin-film bulk acoustic wave resonators (FBAR) sensors operating in shear-mode enable the real-type detection of analytes in fluids, a critical trait missing from many other sensor platforms. Several challenges must be addressed to enable the deployment of FBAR sensors for the assaying of proteins in fluids. First, typical piezoelectric materials employed in such devices tend to degrade when exposed to fluids. Second, the ability to refresh and reuse the sensor surface would constitute an important asset. Finally, the sensor response should be made specific to the detection of the pathogen. This project will address these challenges through the following goals: 1) to develop piezoelectric nanomaterials and FBAR devices resilient to exposure of fluids, 2) to develop refreshable surface moieties imparting specificity to detection of proteins and prions, and 3) to integrate these biologically-enhanced sensors with active CMOS readout circuitry. This platform will open new opportunities for the Canadian health care and pharmaceutical industries. It will enhance the ability of Canadian pharmaceutical industries to develop and market new drugs, allow a better understanding of related diseases, and thus enhance the well-being of Canadians in general.